Prophylactic Use of Maribavir for the Prevention of Cytomegalovirus (CMV) Disease in Stem Cell Transplant Recipients

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00411645
• Collaborator: (none)
• Enrollment: 681
• Locations: 97
• Arms: 2
• Actual Duration (Months): 29.3
• Patients Per Site: 7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this research study is to investigate whether or not maribavir is safe and effective for preventing CMV disease when taken by mouth for up to 12 weeks in patients who have had a stem cell transplant.

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus Infections	Drug: maribavir; Other: placebo	Phase 3

Detailed Description

Cytomegalovirus (CMV) infections remain a significant problem following various types of transplants that are associated with strong immunosuppressive therapy. Maribavir is a new oral anti-CMV drug with a novel mechanism of action compared to currently available anti-CMV drugs. This study will test the safety and efficacy of maribavir for the prevention of CMV disease when given as prophylaxis for up to 12 weeks following allogeneic stem cell transplant.

Study Design

• Study Type: Interventional
• Actual Enrollment: 681 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Prophylactic Use of Maribavir for the Prevention of Cytomegalovirus Disease in Recipients of Allogeneic Stem Cell Transplants.
• Actual Study Start Date: Dec 13, 2006
• Actual Primary Completion Date: Nov 10, 2008
• Actual Study Completion Date: May 23, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: maribavir; 100 mg twice daily for up to 12 weeks
Placebo Comparator: B	Other: placebo; twice daily for up to 12 weeks

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation [6 months post-transplant]

   All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.

Secondary Outcome Measures

1. Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-transplant [6 months post-transplant]

   All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.

2. Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post- Transplantation [6 months post-transplant]

   All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease) were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay or (2) CMV DNA polymerase chain reaction (PCR). CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.

3. Number of Participants With Investigator-determined CMV Disease [Through 12 months post-transplant (Day 1 to 100 days, 6 months, and 12 months post-transplant)]

   CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.

4. Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation [100 days post-transplant]

   All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.

5. Number of Participants With EC-confirmed CMV Disease Within 12 Months Post-Transplantation [12 months post-transplant]

   All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.

6. Percent of Participants With Acute Graft-Versus-Host Disease (GVHD) [Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant)]

   Analysis of acute GVHD was based on reported adverse events that mapped to the relevant MedDRA dictionary terms for acute GVHD. The percentage reported is for the occurrence of any grade of acute GVHD.

7. Percent of Participants With Chronic Graft-Versus-Host Disease (GVHD) [Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant)]

   Analysis of chronic GVHD was based on reported adverse events that mapped to the relevant MedDRA dictionary terms for chronic GVHD. The percentage reported is for the occurrence of any grade of chronic GVHD.

8. Number of Participants Who Died Within 12 Months Post-Transplantation [Through 12 months post-transplant (Days 1 to 100, 6 months, and 12 months post-transplant)]

9. Plasma Concentration of Maribavir During Treatment [12 hours post-dose after 1 and 4 weeks of treatment]

   Pharmacokinetic (PK) profile sampling was performed to evaluate plasma concentrations of Maribavir. During the study drug administration period, blood samples for this purpose were collected on Day 7 (Week 1) and at Week 4. Every effort was made to ensure that doses were administered 12 hours apart on the day before and on the day of PK sampling. Permissible assessment windows for PK profile sampling purposes were +/- 3 days and +/- 5 days for the 1- and 4- week samples, respectively. Samples were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. The validated lower limit of quantitation (LLOQ) in plasma was 0.2 μg/mL.

10. Plasma Concentration of Maribavir Metabolite VP 44469 During Treatment [12 hours post-dose after 1 and 4 weeks of treatment]

    Pharmacokinetic (PK) profile sampling was performed to evaluate plasma concentrations of VP 44469, a metabolite of Maribavir. During the study drug administration period, blood samples for this purpose were collected on Day 7 (Week 1) and at Week 4. Every effort was made to ensure that doses were administered 12 hours apart on the day before and on the day of PK sampling. Permissible assessment windows for PK profile sampling purposes were +/- 3 days and +/- 5 days for the 1- and 4- week samples, respectively. Samples were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. The validated lower limit of quantitation (LLOQ) in plasma was 0.2 μg/mL.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Allogeneic stem cell transplant recipient

• Recipient or donor CMV seropositive

• Have transplant engraftment

• Able to swallow tablets

Exclusion Criteria:

• CMV organ disease

• HIV infection

• Use of other anti-CMV therapy post-transplant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas Myeloma Institute	Little Rock	Arkansas	United States	72205
2	City of Hope Medical Center	Duarte	California	United States	91010
3	Scripps Green Hospital	La Jolla	California	United States	92037
4	UCSD Moores Center	La Jolla	California	United States	92093-0960
5	UCLA Medical Center	Los Angeles	California	United States	90095-1678
6	University of California, San Francisco	San Francisco	California	United States	94143
7	Stanford University Medical Center	Stanford	California	United States	94305
8	Rocky Mountain Cancer Center	Denver	Colorado	United States	80218
9	Shands Hospital	Gainesville	Florida	United States	32610
10	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
11	Emory University	Atlanta	Georgia	United States	30322
12	Northwestern University Medical Center	Chicago	Illinois	United States	60611
13	University of Chicago	Chicago	Illinois	United States	60637
14	Loyola University	Maywood	Illinois	United States	60153
15	St Francis Hospital	Beech Grove	Indiana	United States	46107
16	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
17	University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536
18	University Medical Center University of Louisville Hospital	Louisville	Kentucky	United States	40202
19	Greenbaum Cancer Center	Baltimore	Maryland	United States	21201-1595
20	Massachusettes General	Boston	Massachusetts	United States	02114
21	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
22	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
23	University of Michigan	Ann Arbor	Michigan	United States	48109-0914
24	Wayne State Medical Center	Detroit	Michigan	United States	48201
25	Henry Ford Health System	Detroit	Michigan	United States	48202
26	University of Minnesota	Minneapolis	Minnesota	United States	55455
27	Mayo Clinic College of Medicine	Rochester	Minnesota	United States	55905
28	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
29	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
30	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
31	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
32	New York Presbyterian Hospital,Weill Cornell Medical Center	New York	New York	United States	10021
33	Mount Sinai Hospital	New York	New York	United States	10029
34	University of Rochester Medical Center	Rochester	New York	United States	14642
35	University of North Carolina Hospital	Chapel Hill	North Carolina	United States	27599
36	Duke Medical Center	Durham	North Carolina	United States	27710
37	Wake Forest Medical Center	Winston-Salem	North Carolina	United States	27157
38	The Jewish Hospital	Cincinnati	Ohio	United States	45236
39	Ireland Cancer Center Case Western Reserve University	Cleveland	Ohio	United States	44106
40	University of Oklahoma	Oklahoma City	Oklahoma	United States	73104
41	Oregon Health and Sciences University	Portland	Oregon	United States	97239-3098
42	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
43	Thomas Jefferson	Philadelphia	Pennsylvania	United States	19107
44	Jeanes Hospital - Temple	Philadelphia	Pennsylvania	United States	19111
45	Western Pennsylvania Cancer Institute	Pittsburgh	Pennsylvania	United States	15224
46	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
47	Vanderbilt Medical Center	Nashville	Tennessee	United States	37232
48	Baylor University Medical Center	Dallas	Texas	United States	75246
49	MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
50	Methodist Hospital	Houston	Texas	United States	77030
51	Texas Transplant Institute	San Antonio	Texas	United States	78229
52	Latter Day Saints Hospital	Salt Lake City	Utah	United States	84103
53	Medical College of Virginia	Richmond	Virginia	United States	23298
54	VA Puget Sound Health Center	Seattle	Washington	United States	98108
55	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
56	West Virginia University Hospital	Morgantown	West Virginia	United States	26506-9162
57	ZNA Stuivenberg	Antwerp		Belgium	2060
58	AZ Sint Jan, Department of Hematology	Brugge		Belgium	8000
59	Cliniques Universitaires St,Luc Dept Hematology	Brussels		Belgium	1200
60	UZ Gasthuisberg	Leuven		Belgium	3000
61	CHU Sart -Tilman Department of Medicine, Hematology	Liege		Belgium	4000
62	QEII Health Sciences Center	Halifax	Nova Scotia	Canada	B3H2Y9
63	McMaster University Medical Center	Hamilton	Ontario	Canada	L8N 3Z5
64	London Health Sciences Centre	London	Ontario	Canada	N6A 4G5
65	Ottawa General Campus	Ottawa,	Ontario	Canada	K1H 8L6
66	Hopital l'Enfant Jesus	Quebec		Canada	G1J 1Z4
67	Hopital Henri Mondor	Créteil		France	94010
68	Edouard Herriot Hopital	Lyon, Cedex 03		France	69437
69	Institut Paoli Calmettes	Marseille Cedex 9		France	13273
70	Hopital Hotel Dieu	Nantes, Cedex 1		France	44093
71	Hopital St. Louis	Paris Cedex 10		France	75475
72	Hopital Haut-Leveque	Pessac		France	33600
73	Univ. Clinic Dresden	Dresden		Germany	01307
74	University Clinic of Dresden	Dresden		Germany	01307
75	University of Essen	Essen		Germany	45122
76	University of Freiburg	Freiburg		Germany	79106
77	University of Hamburg-Eppendorf	Hamburg		Germany	20246
78	Hannover, Medizinische Hochschule	Hannover		Germany	30625
79	University of Heidelberg	Heidelberg		Germany	69120
80	Universitaetsklinikum Koeln, Clinic I for internal Medicine	Koeln		Germany	50937
81	Johannes-Gutenberg University	Mainz		Germany	55131
82	University Clinic of Ulm	Ulm		Germany	89081
83	Careggi University Hospital	Firenze		Italy	50134
84	University of San Martino Hospital	Genova		Italy	16132
85	San Raffaele del Monte Tabor	Milano		Italy	20132
86	Pescara Hospital	Pescara		Italy	65123
87	Bianchi-Melacrino-Morelli Hospital	Reggio Calabria		Italy	89100
88	Barcelona Hospital	Barcelona		Spain	08036
89	Duran i Reynals Hospital	Barcelona		Spain	08907
90	University of Salamanca	Salamanca		Spain	E-37007
91	Karolinska University Hospital	Huddinge	Stockholm	Sweden	14186
92	Sahlgrenska University Hospital	Goteborg		Sweden	S-413 45
93	Karolinska University Hospital,Huddinge	Stockholm		Sweden	141 86
94	Akademiska Sjukhuset, Dept Hematology	Uppsala		Sweden	751 85
95	University College Hospital	London		United Kingdom	NW1 2BU
96	Royal Free Hospital	London		United Kingdom	NW3 2QG
97	Hammersmith Hospital	London		United Kingdom	W12 OHS

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT00411645
• Other Study ID Numbers: 1263-300; 2006-005692-18; SHP620-300; NCT00430339
• First Posted: Dec 14, 2006
• Last Update Posted: Jun 11, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Shire: prevention; prophylaxis; Cytomegalovirus; CMV; allogeneic stem cell transplant; SCT
• Additional relevant MeSH terms: Cytomegalovirus Infections; Maribavir

Study Results

Participant Flow

Arm/Group Title	Placebo	Maribavir 100 mg BID
Arm/Group Description	Participants received placebo twice daily (BID) for up to 12 weeks.	Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Period Title: Overall Study
STARTED	227	454
COMPLETED	146	290
NOT COMPLETED	81	164

Baseline Characteristics

Arm/Group Title	Placebo	Maribavir 100 mg BID	Total
Arm/Group Description	Participants received placebo twice daily (BID) for up to 12 weeks.	Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.	Total of all reporting groups
Overall Participants	227	454	681
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49 (13.1)	49 (12.5)	49 (12.7)
Age, Customized (Count of Participants)
18 to 44 years	74 32.6%	136 30%	210 30.8%
45 to 64 years	134 59%	286 63%	420 61.7%
65 to 75 years	18 7.9%	32 7%	50 7.3%
> 75 years	1 0.4%	0 0%	1 0.1%
Sex: Female, Male (Count of Participants)
Female	98 43.2%	189 41.6%	287 42.1%
Male	129 56.8%	265 58.4%	394 57.9%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation
Description	All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
Time Frame	6 months post-transplant

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) population, defined as all participants who were randomized to one of the therapy groups, regardless of whether the participant received study drug or had any post-baseline evaluations.

Arm/Group Title	Placebo	Maribavir 100 mg BID
Arm/Group Description	Participants received placebo twice daily (BID) for up to 12 weeks.	Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Measure Participants	227	454
Number [participants]	11 4.8%	20 4.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.789
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.902
	Confidence Interval	(2-Sided) 95%; 0.424 to 1.920
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus placebo

2. Secondary Outcome

Title	Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-transplant
Description	All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
Time Frame	6 months post-transplant

Outcome Measure Data

Analysis Population Description

The ITT population, defined as all participants who were randomized to one of the therapy groups, regardless of whether the participant received study drug or had any post-baseline evaluations.

Arm/Group Title	Placebo	Maribavir 100 mg BID
Arm/Group Description	Participants received placebo twice daily (BID) for up to 12 weeks.	Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Measure Participants	227	454
pp65 antigenemia assay	88 38.8%	143 31.5%
CMV DNA PCR assay	77 33.9%	152 33.5%
pp65 antigenemia or CMV DNA PCR assay	101 44.5%	183 40.3%
Initiation of anti-CMV therapy	92 40.5%	172 37.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of pp65 antigenemia assay
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.056
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.721
	Confidence Interval	(2-Sided) 95%; 0.515 to 1.008
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of CMV DNA PCR assay
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.904
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.979
	Confidence Interval	(2-Sided) 95%; 0.697 to 1.375
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of pp65 antigenemia or CMV DNA PCR assay
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.289
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.838
	Confidence Interval	(2-Sided) 95%; 0.606 to 1.161
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of initiation of anti-CMV therapy
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.493
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.891
	Confidence Interval	(2-Sided) 95%; 0.640 to 1.239
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus placebo

3. Secondary Outcome

Title	Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post- Transplantation
Description	All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease) were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay or (2) CMV DNA polymerase chain reaction (PCR). CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
Time Frame	6 months post-transplant

Outcome Measure Data

Analysis Population Description

The ITT population, defined as all participants who were randomized to one of the therapy groups, regardless of whether the participant received study drug or had any post-baseline evaluations.

Arm/Group Title	Placebo	Maribavir 100 mg BID
Arm/Group Description	Participants received placebo twice daily (BID) for up to 12 weeks.	Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Measure Participants	227	454
Median (Inter-Quartile Range) [days]	21	22

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.129
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.130
	Comments	The p-value from Wald Chi-Square test for treatment effect.
	Method	Wald Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Adjusted hazard ratio
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.65 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	Maribavir versus placebo; based on Cox's proportional hazards regression model: time = recipient CMV serostatus (R+ or R-) + transplant type (myeloablative or non-myeloablative/reduced intensity) + treatment.

4. Secondary Outcome

Title	Number of Participants With Investigator-determined CMV Disease
Description	CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
Time Frame	Through 12 months post-transplant (Day 1 to 100 days, 6 months, and 12 months post-transplant)

Outcome Measure Data

Analysis Population Description

The ITT population, defined as all participants who were randomized to one of the therapy groups, regardless of whether the participant received study drug or had any post-baseline evaluations.

Arm/Group Title	Placebo	Maribavir 100 mg BID
Arm/Group Description	Participants received placebo twice daily (BID) for up to 12 weeks.	Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Measure Participants	227	454
100 days post-tranplant	6 2.6%	16 3.5%
6 months post-transplant	11 4.8%	26 5.7%
12 months post-transplant	13 5.7%	28 6.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of 100 days post-transplant
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.542
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of 6 months post-transplant
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.637
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of 12 months post-transplant
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.825
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments

5. Secondary Outcome

Title	Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation
Description	All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
Time Frame	100 days post-transplant

Outcome Measure Data

Analysis Population Description

The ITT population, defined as all participants who were randomized to one of the therapy groups, regardless of whether the participant received study drug or had any post-baseline evaluations.

Arm/Group Title	Placebo	Maribavir 100 mg BID
Arm/Group Description	Participants received placebo twice daily (BID) for up to 12 weeks.	Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Measure Participants	227	454
pp65 antigenemia assay	79 34.8%	120 26.4%
CMV DNA PCR assay	69 30.4%	126 27.8%
pp65 antigenemia assay or CMV DNA PCR assay	92 40.5%	157 34.6%
Initiation of anti-CMV therapy	85 37.4%	139 30.6%
EC-confirmed disease	6 2.6%	11 2.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of pp65 antigenemia assay
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.022
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.669
	Confidence Interval	(2-Sided) 95%; 0.474 to 0.946
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of CMV DNA PCR assay
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.468
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.878
	Confidence Interval	(2-Sided) 95%; 0.617 to 1.247
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of pp65 antigenemia assay or CMV DNA PCR assay
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.125
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.772
	Confidence Interval	(2-Sided) 95%; 0.555 to 1.075
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of initiation of anti-CMV therapy
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.069
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.731
	Confidence Interval	(2-Sided) 95%; 0.521 to 1.026
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus placebo

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of EC-confirmed disease
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.860
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.913
	Confidence Interval	(2-Sided) 95%; 0.332 to 2.508
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus placebo

6. Secondary Outcome

Title	Number of Participants With EC-confirmed CMV Disease Within 12 Months Post-Transplantation
Description	All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
Time Frame	12 months post-transplant

Outcome Measure Data

Analysis Population Description

The ITT population, defined as all participants who were randomized to one of the therapy groups, regardless of whether the participant received study drug or had any post-baseline evaluations.

Arm/Group Title	Placebo	Maribavir 100 mg BID
Arm/Group Description	Participants received placebo twice daily (BID) for up to 12 weeks.	Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Measure Participants	227	454
Number [participants]	13 5.7%	22 4.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of 12 months post-transplant
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.617
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R-) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.835
	Confidence Interval	(2-Sided) 95%; 0.411 to 1.693
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus placebo

7. Secondary Outcome

Title	Percent of Participants With Acute Graft-Versus-Host Disease (GVHD)
Description	Analysis of acute GVHD was based on reported adverse events that mapped to the relevant MedDRA dictionary terms for acute GVHD. The percentage reported is for the occurrence of any grade of acute GVHD.
Time Frame	Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant)

Outcome Measure Data

Analysis Population Description

The ITT Safety (ITT-S) population, defined as participants in the ITT population who received at least one dose of study drug.

Arm/Group Title	Placebo	Maribavir 100 mg BID
Arm/Group Description	Participants received placebo twice daily (BID) for up to 12 weeks.	Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Measure Participants	223	451
100 days post-transplant	39 17.2%	40 8.8%
6 months post-transplant	43 18.9%	44 9.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of 100 days post-transplant
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7808
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R -) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.048
	Confidence Interval	(2-Sided) 95%; 0.754 to 1.457
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of 6 months post-transplant
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6946
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R -) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.068
	Confidence Interval	(2-Sided) 95%; 0.771 to 1.479
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus placebo

8. Secondary Outcome

Title	Percent of Participants With Chronic Graft-Versus-Host Disease (GVHD)
Description	Analysis of chronic GVHD was based on reported adverse events that mapped to the relevant MedDRA dictionary terms for chronic GVHD. The percentage reported is for the occurrence of any grade of chronic GVHD.
Time Frame	Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant)

Outcome Measure Data

Analysis Population Description

The ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.

Arm/Group Title	Placebo	Maribavir 100 mg BID
Arm/Group Description	Participants received placebo twice daily (BID) for up to 12 weeks.	Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Measure Participants	223	451
100 days post-transplant	5 2.2%	6 1.3%
6 months post-transplant	25 11%	19 4.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of 100 days post-transplant
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6304
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R -) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.186
	Confidence Interval	(2-Sided) 95%; 0.592 to 2.375
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Maribavir 100 mg BID
	Comments	Analysis of 6 months post-transplant
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1019
	Comments	The p-value is from the Cochran-Mantel-Haenszel test, adjusting for recipient CMV serostatus (R+ or R -) and transplant type (myeloablative or non-myeloablative/reduced intensity).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.726
	Confidence Interval	(2-Sided) 95%; 0.495 to 1.066
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mantel-Haenszel odds ratio for maribavir versus placebo

9. Secondary Outcome

Title	Number of Participants Who Died Within 12 Months Post-Transplantation
Time Frame	Through 12 months post-transplant (Days 1 to 100, 6 months, and 12 months post-transplant)

Outcome Measure Data

Analysis Population Description

The ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.

Arm/Group Title	Placebo	Maribavir 100 mg BID
Arm/Group Description	Participants received placebo twice daily (BID) for up to 12 weeks.	Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Measure Participants	223	451
100 days post-transplant	19 8.4%	30 6.6%
6 months post-transplant	37 16.3%	88 19.4%
12 months post-transplant	59 26%	139 30.6%

10. Secondary Outcome

Title	Plasma Concentration of Maribavir During Treatment
Description	Pharmacokinetic (PK) profile sampling was performed to evaluate plasma concentrations of Maribavir. During the study drug administration period, blood samples for this purpose were collected on Day 7 (Week 1) and at Week 4. Every effort was made to ensure that doses were administered 12 hours apart on the day before and on the day of PK sampling. Permissible assessment windows for PK profile sampling purposes were +/- 3 days and +/- 5 days for the 1- and 4- week samples, respectively. Samples were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. The validated lower limit of quantitation (LLOQ) in plasma was 0.2 μg/mL.
Time Frame	12 hours post-dose after 1 and 4 weeks of treatment

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) population, defined as those participants in the ITT population from whom plasma samples were drawn, tested for maribavir concentrations, and complete, evaluable PK data were available.

Arm/Group Title	Maribavir 100 mg BID
Arm/Group Description	Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Measure Participants	66
1 week post-dose, n=63	2.11 (2.10)
4 weeks post-dose, n=48	2.19 (1.99)

11. Secondary Outcome

Title	Plasma Concentration of Maribavir Metabolite VP 44469 During Treatment
Description	Pharmacokinetic (PK) profile sampling was performed to evaluate plasma concentrations of VP 44469, a metabolite of Maribavir. During the study drug administration period, blood samples for this purpose were collected on Day 7 (Week 1) and at Week 4. Every effort was made to ensure that doses were administered 12 hours apart on the day before and on the day of PK sampling. Permissible assessment windows for PK profile sampling purposes were +/- 3 days and +/- 5 days for the 1- and 4- week samples, respectively. Samples were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. The validated lower limit of quantitation (LLOQ) in plasma was 0.2 μg/mL.
Time Frame	12 hours post-dose after 1 and 4 weeks of treatment

Outcome Measure Data

Analysis Population Description

The PK population, defined as those participants in the ITT population from whom plasma samples were drawn, tested for maribavir concentrations, and complete, evaluable PK data were available.

Arm/Group Title	Maribavir 100 mg BID
Arm/Group Description	Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Measure Participants	66
1 week post-dose, n=63	0.56 (0.36)
4 weeks post-dose, n=48	0.65 (0.47)

Adverse Events

Adverse Event Reporting Description	Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Arm/Group Title	Placebo		Maribavir 100 mg BID
Arm/Group Description	Participants received placebo twice daily (BID) for up to 12 weeks.		Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
All Cause Mortality
	Placebo		Maribavir 100 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Maribavir 100 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	98/223 (43.9%)		197/451 (43.7%)
Blood and lymphatic system disorders
Anaemia	0/223 (0%)		3/451 (0.7%)
Aplasia Pure Red Cell	1/223 (0.4%)		0/451 (0%)
Febrile Neutropenia	6/223 (2.7%)		4/451 (0.9%)
Haemolysis	0/223 (0%)		1/451 (0.2%)
Haemolytic Uraemic Syndrome	0/223 (0%)		1/451 (0.2%)
Leukaemia Recurrent	6/223 (2.7%)		15/451 (3.3%)
Leukopenia	1/223 (0.4%)		1/451 (0.2%)
Lymphoproliferative Disorder	1/223 (0.4%)		5/451 (1.1%)
Myelodysplastic Syndrome	2/223 (0.9%)		1/451 (0.2%)
Myeloma Recurrence	1/223 (0.4%)		0/451 (0%)
Neutropenia	0/223 (0%)		2/451 (0.4%)
Non-Hodgkin's Lymphoma Recurrent	4/223 (1.8%)		5/451 (1.1%)
Pancytopenia	1/223 (0.4%)		4/451 (0.9%)
Relapse of underlying disease	13/223 (5.8%)		21/451 (4.7%)
Thrombocytopenia	1/223 (0.4%)		3/451 (0.7%)
Thrombotic Microangiopathy	0/223 (0%)		2/451 (0.4%)
Thrombotic Thrombocytopenic Purpura	0/223 (0%)		2/451 (0.4%)
Cardiac disorders
Acute Coronary Syndrome	0/223 (0%)		1/451 (0.2%)
Arrhythmia	1/223 (0.4%)		0/451 (0%)
Atrial Fibrillation	1/223 (0.4%)		0/451 (0%)
Cardiac Failure	1/223 (0.4%)		1/451 (0.2%)
Palpitations	0/223 (0%)		1/451 (0.2%)
Pericardial Effusion	0/223 (0%)		3/451 (0.7%)
Supraventricular Tachycardia	0/223 (0%)		1/451 (0.2%)
Gastrointestinal disorders
Abdominal Pain	0/223 (0%)		3/451 (0.7%)
Caecitis	0/223 (0%)		2/451 (0.4%)
Clostridium Difficile Colitis	3/223 (1.3%)		5/451 (1.1%)
Colitis	2/223 (0.9%)		2/451 (0.4%)
Constipation	1/223 (0.4%)		0/451 (0%)
Diarrhoea	1/223 (0.4%)		7/451 (1.6%)
Dyspepsia	1/223 (0.4%)		0/451 (0%)
Dysphagia	0/223 (0%)		1/451 (0.2%)
Eosinophilic Colitis	0/223 (0%)		1/451 (0.2%)
Gastritis	2/223 (0.9%)		0/451 (0%)
Gastritis Haemorrhagic	0/223 (0%)		1/451 (0.2%)
Gastroenteritis Caliciviral	0/223 (0%)		1/451 (0.2%)
Gastroenteritis Viral	1/223 (0.4%)		0/451 (0%)
Gastrointestinal Haemorrhage	1/223 (0.4%)		2/451 (0.4%)
Gingivitis	0/223 (0%)		1/451 (0.2%)
Helicobacter Gastritis	1/223 (0.4%)		0/451 (0%)
Ileus	1/223 (0.4%)		0/451 (0%)
Intra-Abdominal Haemorrhage	1/223 (0.4%)		0/451 (0%)
Lactose Intolerance	1/223 (0.4%)		0/451 (0%)
Nausea	2/223 (0.9%)		4/451 (0.9%)
Peritonitis Bacterial	1/223 (0.4%)		0/451 (0%)
Rectal Haemorrhage	0/223 (0%)		1/451 (0.2%)
Rectal Lesion	1/223 (0.4%)		0/451 (0%)
Vomiting	4/223 (1.8%)		5/451 (1.1%)
General disorders
Catheter Site Infection	0/223 (0%)		1/451 (0.2%)
General Physical Health Deterioration	0/223 (0%)		1/451 (0.2%)
Multi-Organ Failure	2/223 (0.9%)		2/451 (0.4%)
Pyrexia	14/223 (6.3%)		28/451 (6.2%)
Hepatobiliary disorders
Cholecystitis	0/223 (0%)		2/451 (0.4%)
Cholelithiasis	0/223 (0%)		1/451 (0.2%)
Cholestasis	1/223 (0.4%)		0/451 (0%)
Hepatic Encephalopathy	1/223 (0.4%)		0/451 (0%)
Hepatic Failure	0/223 (0%)		3/451 (0.7%)
Hepatitis Viral	1/223 (0.4%)		0/451 (0%)
Hepatotoxicity	0/223 (0%)		1/451 (0.2%)
Venoocclusive Liver Disease	2/223 (0.9%)		1/451 (0.2%)
Immune system disorders
Acute Graft Versus Host Disease	25/223 (11.2%)		56/451 (12.4%)
Chronic Graft Versus Host Disease	1/223 (0.4%)		1/451 (0.2%)
Infections and infestations
Acinetobacter Bacteraemia	0/223 (0%)		1/451 (0.2%)
Adenovirus Infection	0/223 (0%)		1/451 (0.2%)
Aspergillosis	0/223 (0%)		1/451 (0.2%)
Bacteraemia	3/223 (1.3%)		9/451 (2%)
Bacterial Sepsis	0/223 (0%)		1/451 (0.2%)
Bk Virus Infection	3/223 (1.3%)		1/451 (0.2%)
Catheter Sepsis	1/223 (0.4%)		0/451 (0%)
Central Line Infection	3/223 (1.3%)		3/451 (0.7%)
Cytomegalovirus Gastroenteritis	4/223 (1.8%)		6/451 (1.3%)
Cytomegalovirus Infection	4/223 (1.8%)		10/451 (2.2%)
Enterococcal Bacteraemia	1/223 (0.4%)		1/451 (0.2%)
Enterococcal Sepsis	0/223 (0%)		2/451 (0.4%)
Epstein-Barr Virus Infection	1/223 (0.4%)		3/451 (0.7%)
Escherichia Bacteraemia	1/223 (0.4%)		0/451 (0%)
Herpes Dermatitis	0/223 (0%)		1/451 (0.2%)
Herpes Zoster	0/223 (0%)		1/451 (0.2%)
Human Herpesvirus 6 Infection	1/223 (0.4%)		0/451 (0%)
Human Polyomavirus Infection	0/223 (0%)		1/451 (0.2%)
Klebsiella Bacteraemia	0/223 (0%)		2/451 (0.4%)
Klebsiella Sepsis	1/223 (0.4%)		0/451 (0%)
Oral Herpes	0/223 (0%)		1/451 (0.2%)
Pneumonia Cytomegaloviral	1/223 (0.4%)		6/451 (1.3%)
Pseudomonal Bacteraemia	0/223 (0%)		3/451 (0.7%)
Salmonella Sepsis	1/223 (0.4%)		0/451 (0%)
Sepsis	2/223 (0.9%)		2/451 (0.4%)
Serratia Bacteraemia	1/223 (0.4%)		2/451 (0.4%)
Staphylococcal Bacteraemia	3/223 (1.3%)		9/451 (2%)
Staphylococcal Sepsis	0/223 (0%)		2/451 (0.4%)
Streptococcal Bacteraemia	1/223 (0.4%)		0/451 (0%)
Urosepsis	0/223 (0%)		1/451 (0.2%)
Zygomycosis	1/223 (0.4%)		2/451 (0.4%)
Injury, poisoning and procedural complications
Blood Stem Cell Transplant Failure	1/223 (0.4%)		3/451 (0.7%)
Incision Site Infection	0/223 (0%)		1/451 (0.2%)
Infusion Related Reaction	0/223 (0%)		1/451 (0.2%)
Post Procedural Haematoma	0/223 (0%)		1/451 (0.2%)
Therapeutic Agent Toxicity	1/223 (0.4%)		3/451 (0.7%)
Transfusion Reaction	0/223 (0%)		2/451 (0.4%)
Investigations
Blood Creatinine Increased	1/223 (0.4%)		1/451 (0.2%)
Blood Uric Acid Increased	0/223 (0%)		1/451 (0.2%)
Hepatic Enzyme Increased	0/223 (0%)		3/451 (0.7%)
International Normalised Ratio Increased	0/223 (0%)		1/451 (0.2%)
Metabolism and nutrition disorders
Anorexia	0/223 (0%)		2/451 (0.4%)
Dehydration	0/223 (0%)		3/451 (0.7%)
Electrolyte Imbalance	1/223 (0.4%)		0/451 (0%)
Failure To Thrive	0/223 (0%)		1/451 (0.2%)
Hyperglycaemia	0/223 (0%)		4/451 (0.9%)
Hyperkalaemia	1/223 (0.4%)		0/451 (0%)
Hypertriglyceridaemia	0/223 (0%)		1/451 (0.2%)
Hypovolaemia	0/223 (0%)		1/451 (0.2%)
Lactic Acidosis	0/223 (0%)		1/451 (0.2%)
Musculoskeletal and connective tissue disorders
Haemarthrosis	0/223 (0%)		1/451 (0.2%)
Muscle Abscess	0/223 (0%)		1/451 (0.2%)
Myopathy Steroid	0/223 (0%)		1/451 (0.2%)
Myositis	1/223 (0.4%)		0/451 (0%)
Pain In Extremity	2/223 (0.9%)		0/451 (0%)
Rhabdomyolysis	0/223 (0%)		1/451 (0.2%)
Spinal Compression Fracture	0/223 (0%)		1/451 (0.2%)
Staphylococcal Osteomyelitis	1/223 (0.4%)		0/451 (0%)
Nervous system disorders
Arachnoiditis	0/223 (0%)		1/451 (0.2%)
Cerebral Haemorrhage	0/223 (0%)		1/451 (0.2%)
Convulsion	1/223 (0.4%)		0/451 (0%)
Encephalopathy	0/223 (0%)		3/451 (0.7%)
Extrapyramidal Disorder	0/223 (0%)		1/451 (0.2%)
Guillain-Barre Syndrome	0/223 (0%)		1/451 (0.2%)
Meningitis Aseptic	0/223 (0%)		1/451 (0.2%)
Meningitis Enterococcal	1/223 (0.4%)		0/451 (0%)
Meningitis Viral	0/223 (0%)		1/451 (0.2%)
Metabolic Encephalopathy	1/223 (0.4%)		1/451 (0.2%)
Subarachnoid Haemorrhage	0/223 (0%)		1/451 (0.2%)
Subdural Haematoma	0/223 (0%)		1/451 (0.2%)
Tremor	1/223 (0.4%)		0/451 (0%)
Psychiatric disorders
Depression	0/223 (0%)		1/451 (0.2%)
Mental Status Changes	1/223 (0.4%)		1/451 (0.2%)
Renal and urinary disorders
Cystitis Haemorrhagic	1/223 (0.4%)		3/451 (0.7%)
Dysuria	0/223 (0%)		1/451 (0.2%)
Nephrolithiasis	0/223 (0%)		1/451 (0.2%)
Renal Failure	4/223 (1.8%)		14/451 (3.1%)
Renal Impairment	0/223 (0%)		2/451 (0.4%)
Urinary Tract Infection	2/223 (0.9%)		2/451 (0.4%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome	2/223 (0.9%)		1/451 (0.2%)
Bronchopulmonary Aspergillosis	2/223 (0.9%)		0/451 (0%)
Dyspnoea	0/223 (0%)		1/451 (0.2%)
Hypoxia	1/223 (0.4%)		0/451 (0%)
Influenza	2/223 (0.9%)		2/451 (0.4%)
Lung Infection Pseudomonal	0/223 (0%)		1/451 (0.2%)
Lung Infiltration	0/223 (0%)		2/451 (0.4%)
Parainfluenzae Virus Infection	0/223 (0%)		1/451 (0.2%)
Pleural Effusion	0/223 (0%)		2/451 (0.4%)
Pneumonia	2/223 (0.9%)		4/451 (0.9%)
Pneumonia Fungal	0/223 (0%)		2/451 (0.4%)
Pneumonia Streptococcal	1/223 (0.4%)		0/451 (0%)
Pneumonitis	1/223 (0.4%)		2/451 (0.4%)
Pulmonary Alveolar Haemorrhage	0/223 (0%)		2/451 (0.4%)
Respiratory Failure	0/223 (0%)		2/451 (0.4%)
Respiratory Syncytial Virus Infection	0/223 (0%)		2/451 (0.4%)
Sinusitis	1/223 (0.4%)		0/451 (0%)
Upper Respiratory Tract Infection	1/223 (0.4%)		0/451 (0%)
Skin and subcutaneous tissue disorders
Cellulitis	0/223 (0%)		1/451 (0.2%)
Erythema	1/223 (0.4%)		0/451 (0%)
Rash	0/223 (0%)		1/451 (0.2%)
Skin Exfoliation	1/223 (0.4%)		0/451 (0%)
Vascular disorders
Catheter Thrombosis	1/223 (0.4%)		0/451 (0%)
Deep Vein Thrombosis	0/223 (0%)		3/451 (0.7%)
Hypotension	0/223 (0%)		2/451 (0.4%)
Microangiopathy	0/223 (0%)		1/451 (0.2%)
Orthostatic Hypotension	0/223 (0%)		3/451 (0.7%)
Syncope	1/223 (0.4%)		2/451 (0.4%)
Other (Not Including Serious) Adverse Events
	Placebo		Maribavir 100 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	192/223 (86.1%)		408/451 (90.5%)
Blood and lymphatic system disorders
Anaemia	17/223 (7.6%)		60/451 (13.3%)
Neutropenia	18/223 (8.1%)		33/451 (7.3%)
Thrombocytopenia	16/223 (7.2%)		33/451 (7.3%)
Gastrointestinal disorders
Abdominal Pain	17/223 (7.6%)		34/451 (7.5%)
Constipation	10/223 (4.5%)		41/451 (9.1%)
Diarrhoea	41/223 (18.4%)		86/451 (19.1%)
Dry Mouth	11/223 (4.9%)		41/451 (9.1%)
Dysgeusia	13/223 (5.8%)		66/451 (14.6%)
Dyspepsia	13/223 (5.8%)		16/451 (3.5%)
Nausea	33/223 (14.8%)		68/451 (15.1%)
Oral Candidiasis	10/223 (4.5%)		34/451 (7.5%)
Vomiting	27/223 (12.1%)		48/451 (10.6%)
General disorders
Fatigue	22/223 (9.9%)		73/451 (16.2%)
Oedema Peripheral	28/223 (12.6%)		58/451 (12.9%)
Pyrexia	28/223 (12.6%)		46/451 (10.2%)
Immune system disorders
Acute Graft Versus Host Disease	50/223 (22.4%)		117/451 (25.9%)
Infections and infestations
Bk Virus Infection	13/223 (5.8%)		33/451 (7.3%)
Staphylococcal Bacteraemia	15/223 (6.7%)		17/451 (3.8%)
Investigations
Hepatic Enzyme Increased	15/223 (6.7%)		31/451 (6.9%)
Weight Decreased	29/223 (13%)		41/451 (9.1%)
Metabolism and nutrition disorders
Anorexia	11/223 (4.9%)		26/451 (5.8%)
Hyperglycaemia	10/223 (4.5%)		30/451 (6.7%)
Musculoskeletal and connective tissue disorders
Back Pain	9/223 (4%)		26/451 (5.8%)
Nervous system disorders
Dizziness	11/223 (4.9%)		26/451 (5.8%)
Headache	21/223 (9.4%)		44/451 (9.8%)
Insomnia	16/223 (7.2%)		27/451 (6%)
Tremor	16/223 (7.2%)		32/451 (7.1%)
Renal and urinary disorders
Renal Failure	16/223 (7.2%)		33/451 (7.3%)
Urinary Tract Infection	9/223 (4%)		28/451 (6.2%)
Respiratory, thoracic and mediastinal disorders
Cough	11/223 (4.9%)		35/451 (7.8%)
Upper Respiratory Tract Infection	9/223 (4%)		25/451 (5.5%)
Skin and subcutaneous tissue disorders
Erythema	13/223 (5.8%)		21/451 (4.7%)
Pruritus	14/223 (6.3%)		20/451 (4.4%)
Rash	30/223 (13.5%)		59/451 (13.1%)
Vascular disorders
Hypertension	13/223 (5.8%)		43/451 (9.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.